Our major objective, as in the past 13 years will be to correlate alimentary tract structure with function in health and disease. We will maintain alimentary tract biopsies in vitro in organ culture for up to 48 hours. We will compare epithelial cell proliferation and migration, protein and glycoprotein synthesis and secretion in cultured normal mucosa and cultured gastric mucosa from patients with gastric ulcer, non-atrophic gastritis, and atrophic gastritis and duodenal mucosa from patients with duodenal ulcer. We will use light microscopic, electron microscopic, radioautographic, histochemical and when appropriate biochemical techniques. We will examine the histopathology of the rectal mucosa in acute infectious nonbacterial gastroenteritis induced with Norwalk agent. We will use organ culture to attempt to define the site of viral proliferation within the intestinal mucosa in Norwalk agent-induced acute infectious nonbacterial gastroenteritis. We will prepare enriched preparations of Norwalk agent from infectious fecal filtrates, attempt to radiolabel the virus and determine whether selective intestinal binding plays a role in determining whether the specific individuals are susceptible or immune to this disease. We will use freeze-fracture methodology to examine junctional complexes in selected intestinal diseases associated with excessive intestinal secretion such as celiac-sprue. We will also use freeze fracture methodology to examine junctional complexes in developing fetal rat small intestine during organogenesis. We will utilize organ cultures of rat fetal stomach and small intestine to study humoral factors which may modulate alimentary organogenesis and maturation. Finally, we will determine the time of appearance, specific activity and binding kinetics of corticosteroid recetors in the cytosol of developing rat alimentary tissue and correlate these observations with the morphological and functional development of these tissues.